The Program Project's focus os on the assessment of the efficacy of sentinel lymph node dissection (SLND) in high-risk AJCC Stage II patients enrolled in the multi-center trial (MSLT). Accurate identification and analysis of the sentinel node can improve disease staging and guide further treatment. However, better methods are needed for the detection of metastatic disease and prediction of relapse in early-stage patients. The melanoma lesion, sentinel lymph node and blood of patients undergoing SLND are valuable resource for assessing new molecular methodologies. The project will focus on developing new molecular approaches to improve detection of metastatic disease in blood and sentinel lymph nodes. Melanoma markers developed for RT-PCR and automated Souther blot analysis will be used to evaluate blood and sentinel lymph nodes. We will assess the clinical utility of these molecular markers for detection of subclinical disease and prediction of relapse using blood specimens from SLND patients. We will also use melanoma marker RT-PCR to detect metastasis in frozen and archival paraffin selection of sentinel lymph nodes. The main objective will be to improve detection of micrometastic disease in sentinel lymph nodes. The main objective will be to improve detection of micrometastatic disease in sentinel lymph nodes and recurrent subclinical disease in blood to determine their potential clinicopathological utility in disease staging and prognosis. A method has been developed to asses tumor- specific DNA markers in serum. These markers will be assessed as tumor progression indicators using prospective and archival serum. The objective will be to identify patients with high potential for developing aggressive disease. The MSLT archival and prospective specimens along with their clinical follow up provide a unique resource to validate and determine clinical utility of these new molecular approaches.